In less than 10 years since its inception, RNA interference （RNAi） has had extraordinary impact on biomedical science. RNAi has been demonstrated to influence numerous biological and disease pathways. Development an...In less than 10 years since its inception, RNA interference （RNAi） has had extraordinary impact on biomedical science. RNAi has been demonstrated to influence numerous biological and disease pathways. Development and adoption of RNAi technologies have been prolific ranging from basic loss-of-function tools, genome-wide screening libraries to pharmaceutical target validation and therapeutic development. However, understanding of the molecular mechanisms of RNAi is far from complete. The purpose of this brief review is to highlight key achievements in elucidating the bio- chemical mechanisms of the RNA-induced silencing complex and to outline major challenges for the field.展开更多
Severe acute respiratory syndrome coronavirus 2(SARS-Co V-2) relies on the central molecular machine RNA-dependent RNA polymerase(Rd Rp) for the viral replication and transcription. Remdesivir at the template strand h...Severe acute respiratory syndrome coronavirus 2(SARS-Co V-2) relies on the central molecular machine RNA-dependent RNA polymerase(Rd Rp) for the viral replication and transcription. Remdesivir at the template strand has been shown to effectively inhibit the RNA synthesis in SARS-Co V-2 Rd Rp by deactivating not only the complementary UTP incorporation but also the next nucleotide addition. However, the underlying molecular mechanism of the second inhibitory point remains unclear. In this work, we have performed molecular dynamics simulations and demonstrated that such inhibition has not directly acted on the nucleotide addition at the active site. Instead, the translocation of Remdesivir from +1 to-1 site is hindered thermodynamically as the posttranslocation state is less stable than the pre-translocation state due to the motif B residue G683. Moreover, another conserved residue S682 on motif B further hinders the dynamic translocation of Remdesivir due to the steric clash with the 1′-cyano substitution. Overall,our study has unveiled an alternative role of motif B in mediating the translocation when Remdesivir is present in the template strand and complemented our understanding about the inhibitory mechanisms exerted by Remdesivir on the RNA synthesis in SARS-Co V-2 Rd Rp.展开更多
Objective: To explore the impact of s-phase kinase-associated protein 2 (Skp2) on cervical cancer cell proliferation and the relationship between Skp2 and expression of cell regulation factors and transcription factor...Objective: To explore the impact of s-phase kinase-associated protein 2 (Skp2) on cervical cancer cell proliferation and the relationship between Skp2 and expression of cell regulation factors and transcription factors. Methods: RNAi technology was used to silence Skp2 gene in HeLa cells. After interference, RT-PCR was used for detection of Skp-2 mRNA, and Western blotting and flow cytometry were used for protein expression analysis. Results: siRNA significantly inhibited HeLa cell proliferation (P<0.05) and increased HeLa apoptosis, and G1/G0 phase cells were increased significantly (P<0.01). Skp2 siRNA transfected HeLa cells effectively reduced Skp2 protein levels, while p27 and p-p53 protein levels were increased significantly. RT-PCR results showed that after interference Skp2 mRNA, c-myc mRNA and cyclin A mRNA expressions decreased significantly compared with those in control group (P<0.01), and p27mRNA expression level was significantly higher (P<0.01). Conclusion: The change of Skp2 expression affects the expression of the cell cycle protein, thus affecting proliferation and apoptosis of HeLa cells. Skp2 protein plays an important role in the progression of cervical cancer; yet the specific mechanism still needs further study.展开更多
Life depends on negative entropy, and the growth of plants depends on the negative entropy flow of sunlight and the ecological environment. Plants are fixed on the ground, cannot actively escape from the external haza...Life depends on negative entropy, and the growth of plants depends on the negative entropy flow of sunlight and the ecological environment. Plants are fixed on the ground, cannot actively escape from the external hazards, and thus relies on some of their own response mechanism to defend against various external stress. Due to the limited responsiveness of the plants, the negative entropy operation of the open system is hindered, which results in the death of plants in a large number.Epigenetic regulation plays an important role in this response mechanism, mainly in DNA methylation, histone modification, chromatin remodeling, and noncoding RNA. In this paper, the regulation mechanism of epigenetic modification under various stresses and the analysis of entropy were reviewed, providing a basis for the study of crop resistance.展开更多
Triple-negative breast cancer(TNBC)is currently the most malignant subtype of breast cancer without effective targeted therapies,which makes its pathogenesis an important target for research.A growing number of studie...Triple-negative breast cancer(TNBC)is currently the most malignant subtype of breast cancer without effective targeted therapies,which makes its pathogenesis an important target for research.A growing number of studies have shown that non-coding RNA(ncRNA),including microRNA(miRNA)and long non-coding RNA(lncRNA),plays a significant role in tumorigenesis.This review summarizes the roles of miRNA and lncRNA in the progression,diagnosis,and neoadjuvant chemotherapy of TNBC.Aberrantly expressed miRNA and lncRNA are listed according to their roles.Further,it describes the multiple mechanisms that lncRNA shows for regulating gene expression in the nucleus and cytoplasm,and more importantly,describes lnc RNA-regulated TNBC progression through complete combining with miRNA at the post-transcriptional level.Focusing on miRNA and lncRNA associated with TNBC can provide new insights for early diagnosis and treatment—they can be targeted in the future as a novel anticancer target of TNBC.展开更多
Emerging studies support that RNA-binding proteins （RBPs） play critical roles in human biology and pathogenesis. RBPs are essential players in RNA processing and metabolism, including pre-mRNA splicing, polyadenylat...Emerging studies support that RNA-binding proteins （RBPs） play critical roles in human biology and pathogenesis. RBPs are essential players in RNA processing and metabolism, including pre-mRNA splicing, polyadenylation, transport, surveillance, mRNA localization, mRNA stability control, translational control and editing of various types of RNAs. Aberrant expression of and mutations in RBP genes affect various steps of RNA processing, altering target gene function. RBPs have been associ- ated with various diseases, including neurological diseases. Here, we mainly focus on selected RNA-binding proteins including Nova-i/Nova-2, HuR/HuB/HuC/HuD, TDP-43, Fus, Rbfoxl/Rbfox2, QKI and FMRP, discussing their function and roles in human diseases.展开更多
Antisense RNA molecule represents a unique type of DNA transcript that comprises 19-23 nucleotides and is complementary to mRNA. Antisense RNAs play the crucial role in regulating gene expression at multiple levels, s...Antisense RNA molecule represents a unique type of DNA transcript that comprises 19-23 nucleotides and is complementary to mRNA. Antisense RNAs play the crucial role in regulating gene expression at multiple levels, such as at replication, transcription, and translation. In addition, artificial antisense RNAs can effectively regulate the expression of related genes in host cells. With the development of antisense RNA, investigating the functions of antisense RNAs has emerged as a hot research field. This review summarizes our current understanding of antisense RNAs, particularly of the formation of antisense RNAs and their mechanism of regulating the expression of their target genes. In addition, we detail the effects and applications of antisense RNAs in antivirus and anticancer treatments and in regulating the expression of related genes in plants and microorganisms. This review is intended to highlight the key role of antisense RNA in genetic research and guide new investigators to the study of antisense RNAs.展开更多
The pervasive transcription of the genome creates many types of non-coding RNAs(nc RNAs).However,we know very little regarding the functions and the regulatory mechanisms of these nc RNAs.Exploring the interactions of...The pervasive transcription of the genome creates many types of non-coding RNAs(nc RNAs).However,we know very little regarding the functions and the regulatory mechanisms of these nc RNAs.Exploring the interactions of RNA and RNA binding proteins(RBPs) is vital because it can allow us to truly understand how these nc RNAs behave in vivo.High-throughput sequencing of RNA isolated by cross-linking immunoprecipitation(HITS-CLIP or CLIP-seq) and its variants have been successfully used as systemic techniques to study RBP binding sites.In this review,we will explain the major differences between the CLIP techniques,summarize successful applications of these techniques,discuss limitations of CLIP,present some suggested solutions and project their promising future roles in studying the RNA world.展开更多
A key to tackling the coronavirus disease 2019(COVID-19)pandemic is to understand how severe acute respiratory syndrome coronavirus 2(SARS-Co V-2)manages to outsmart host antiviral defense mechanisms.Stress granules(S...A key to tackling the coronavirus disease 2019(COVID-19)pandemic is to understand how severe acute respiratory syndrome coronavirus 2(SARS-Co V-2)manages to outsmart host antiviral defense mechanisms.Stress granules(SGs),which are assembled during viral infection and function to sequester host and viral m RNAs and proteins,are part of the antiviral responses.Here,we show that the SARS-Co V-2 nucleocapsid(N)protein,an RNA binding protein essential for viral production,interacted with RasGTPase-activating protein SH3-domain-binding protein(G3 BP)and disrupted SG assembly,both of which require intrinsically disordered region1(IDR1)in N protein.The N protein partitioned into SGs through liquid-liquid phase separation with G3 BP,and blocked the interaction of G3 BP1 with other SG-related proteins.Moreover,the N protein domains important for phase separation with G3 BP and SG disassembly were required for SARS-Co V-2 viral production.We propose that N protein-mediated SG disassembly is crucial for SARS-Co V-2 production.展开更多
文摘In less than 10 years since its inception, RNA interference （RNAi） has had extraordinary impact on biomedical science. RNAi has been demonstrated to influence numerous biological and disease pathways. Development and adoption of RNAi technologies have been prolific ranging from basic loss-of-function tools, genome-wide screening libraries to pharmaceutical target validation and therapeutic development. However, understanding of the molecular mechanisms of RNAi is far from complete. The purpose of this brief review is to highlight key achievements in elucidating the bio- chemical mechanisms of the RNA-induced silencing complex and to outline major challenges for the field.
基金supported by the National Key RD program of China(No.2021YFA1502300)the National Natural Science Foundation of China(No.21733007)。
文摘Severe acute respiratory syndrome coronavirus 2(SARS-Co V-2) relies on the central molecular machine RNA-dependent RNA polymerase(Rd Rp) for the viral replication and transcription. Remdesivir at the template strand has been shown to effectively inhibit the RNA synthesis in SARS-Co V-2 Rd Rp by deactivating not only the complementary UTP incorporation but also the next nucleotide addition. However, the underlying molecular mechanism of the second inhibitory point remains unclear. In this work, we have performed molecular dynamics simulations and demonstrated that such inhibition has not directly acted on the nucleotide addition at the active site. Instead, the translocation of Remdesivir from +1 to-1 site is hindered thermodynamically as the posttranslocation state is less stable than the pre-translocation state due to the motif B residue G683. Moreover, another conserved residue S682 on motif B further hinders the dynamic translocation of Remdesivir due to the steric clash with the 1′-cyano substitution. Overall,our study has unveiled an alternative role of motif B in mediating the translocation when Remdesivir is present in the template strand and complemented our understanding about the inhibitory mechanisms exerted by Remdesivir on the RNA synthesis in SARS-Co V-2 Rd Rp.
文摘Objective: To explore the impact of s-phase kinase-associated protein 2 (Skp2) on cervical cancer cell proliferation and the relationship between Skp2 and expression of cell regulation factors and transcription factors. Methods: RNAi technology was used to silence Skp2 gene in HeLa cells. After interference, RT-PCR was used for detection of Skp-2 mRNA, and Western blotting and flow cytometry were used for protein expression analysis. Results: siRNA significantly inhibited HeLa cell proliferation (P<0.05) and increased HeLa apoptosis, and G1/G0 phase cells were increased significantly (P<0.01). Skp2 siRNA transfected HeLa cells effectively reduced Skp2 protein levels, while p27 and p-p53 protein levels were increased significantly. RT-PCR results showed that after interference Skp2 mRNA, c-myc mRNA and cyclin A mRNA expressions decreased significantly compared with those in control group (P<0.01), and p27mRNA expression level was significantly higher (P<0.01). Conclusion: The change of Skp2 expression affects the expression of the cell cycle protein, thus affecting proliferation and apoptosis of HeLa cells. Skp2 protein plays an important role in the progression of cervical cancer; yet the specific mechanism still needs further study.
基金Supported by National Natural Science Foundation of China(51467014)
文摘Life depends on negative entropy, and the growth of plants depends on the negative entropy flow of sunlight and the ecological environment. Plants are fixed on the ground, cannot actively escape from the external hazards, and thus relies on some of their own response mechanism to defend against various external stress. Due to the limited responsiveness of the plants, the negative entropy operation of the open system is hindered, which results in the death of plants in a large number.Epigenetic regulation plays an important role in this response mechanism, mainly in DNA methylation, histone modification, chromatin remodeling, and noncoding RNA. In this paper, the regulation mechanism of epigenetic modification under various stresses and the analysis of entropy were reviewed, providing a basis for the study of crop resistance.
基金Project supported by the Zhejiang Provincial Natural Science Foundation of China(No.LY18C050006)the Key Research and Development Project of Zhejiang Province(No.2020C02039)。
文摘Triple-negative breast cancer(TNBC)is currently the most malignant subtype of breast cancer without effective targeted therapies,which makes its pathogenesis an important target for research.A growing number of studies have shown that non-coding RNA(ncRNA),including microRNA(miRNA)and long non-coding RNA(lncRNA),plays a significant role in tumorigenesis.This review summarizes the roles of miRNA and lncRNA in the progression,diagnosis,and neoadjuvant chemotherapy of TNBC.Aberrantly expressed miRNA and lncRNA are listed according to their roles.Further,it describes the multiple mechanisms that lncRNA shows for regulating gene expression in the nucleus and cytoplasm,and more importantly,describes lnc RNA-regulated TNBC progression through complete combining with miRNA at the post-transcriptional level.Focusing on miRNA and lncRNA associated with TNBC can provide new insights for early diagnosis and treatment—they can be targeted in the future as a novel anticancer target of TNBC.
基金Zhou HuaLin is supported by National Basic Research Program of China(2013CB917803)research fund for the State Key Laboratory of Cog-nitive Neuroscience and Learning from Institute of Biophysics,Chinese Academy of Sciences(7Y1SNY7007)+3 种基金supported by the Ross Maclean Senior Research Fellowship and the Peter Goodenough BequestZhu Li and Liu JiangHong are supported by grants from the Na-tional Major Basic Research Program of China(2010CB529603)the National Natural Science Foundation of China(91132710,31200561)Jane Y.Wu is supported by the US National Institutes of Health
文摘Emerging studies support that RNA-binding proteins （RBPs） play critical roles in human biology and pathogenesis. RBPs are essential players in RNA processing and metabolism, including pre-mRNA splicing, polyadenylation, transport, surveillance, mRNA localization, mRNA stability control, translational control and editing of various types of RNAs. Aberrant expression of and mutations in RBP genes affect various steps of RNA processing, altering target gene function. RBPs have been associ- ated with various diseases, including neurological diseases. Here, we mainly focus on selected RNA-binding proteins including Nova-i/Nova-2, HuR/HuB/HuC/HuD, TDP-43, Fus, Rbfoxl/Rbfox2, QKI and FMRP, discussing their function and roles in human diseases.
基金Project supported by the Natural Science Foundation of Jiangsu Province(No.BK20150149)the China Postdoctoral Science Foundation Grant(No.2016M590410)the Fundamental Research Funds for the Central Universities(No.JUSRP115A19),China
文摘Antisense RNA molecule represents a unique type of DNA transcript that comprises 19-23 nucleotides and is complementary to mRNA. Antisense RNAs play the crucial role in regulating gene expression at multiple levels, such as at replication, transcription, and translation. In addition, artificial antisense RNAs can effectively regulate the expression of related genes in host cells. With the development of antisense RNA, investigating the functions of antisense RNAs has emerged as a hot research field. This review summarizes our current understanding of antisense RNAs, particularly of the formation of antisense RNAs and their mechanism of regulating the expression of their target genes. In addition, we detail the effects and applications of antisense RNAs in antivirus and anticancer treatments and in regulating the expression of related genes in plants and microorganisms. This review is intended to highlight the key role of antisense RNA in genetic research and guide new investigators to the study of antisense RNAs.
基金supported by the National Natural Science Foundation of China(31200593,31230042)the Guangdong Natural Science Foundation (S2011040001760)+1 种基金the Fundamental Research Funds for the Central Universities (13lgpy40)the National Basic Research Program of China (2011CB811300)
文摘The pervasive transcription of the genome creates many types of non-coding RNAs(nc RNAs).However,we know very little regarding the functions and the regulatory mechanisms of these nc RNAs.Exploring the interactions of RNA and RNA binding proteins(RBPs) is vital because it can allow us to truly understand how these nc RNAs behave in vivo.High-throughput sequencing of RNA isolated by cross-linking immunoprecipitation(HITS-CLIP or CLIP-seq) and its variants have been successfully used as systemic techniques to study RBP binding sites.In this review,we will explain the major differences between the CLIP techniques,summarize successful applications of these techniques,discuss limitations of CLIP,present some suggested solutions and project their promising future roles in studying the RNA world.
基金supported by the National Natural Science Foundation of China(81830004,31970755,and 31970173)the Local Grant(608285568031)。
文摘A key to tackling the coronavirus disease 2019(COVID-19)pandemic is to understand how severe acute respiratory syndrome coronavirus 2(SARS-Co V-2)manages to outsmart host antiviral defense mechanisms.Stress granules(SGs),which are assembled during viral infection and function to sequester host and viral m RNAs and proteins,are part of the antiviral responses.Here,we show that the SARS-Co V-2 nucleocapsid(N)protein,an RNA binding protein essential for viral production,interacted with RasGTPase-activating protein SH3-domain-binding protein(G3 BP)and disrupted SG assembly,both of which require intrinsically disordered region1(IDR1)in N protein.The N protein partitioned into SGs through liquid-liquid phase separation with G3 BP,and blocked the interaction of G3 BP1 with other SG-related proteins.Moreover,the N protein domains important for phase separation with G3 BP and SG disassembly were required for SARS-Co V-2 viral production.We propose that N protein-mediated SG disassembly is crucial for SARS-Co V-2 production.
